The degradation of various constituents of the extracellular matrix including, heparan sulfate proteoglycans, represents a critical step in the process of cancer invasion and metastasis. Heparanase, an endo-p-D- glycosidase which degrades HS, has emerged as a promising target for the development of anti-cancer treatment because of its pro-metastatic, pro-inflammatory, and pro-angiogenic activity. Therefore we sought to utilize a novel enzymatic approach to probe the specificity of heparanase and its inhibitor.